Inactive caspase 3 activates Akt in human leukemia cells susceptible or resistant to apoptosis induced by phorbol ester

  • Authors:
    • Jeong-Ok Hah
    • Kyung-Ah Lee
    • Yun Jung Choi
    • Won-Duck Kim
    • Jong-Wook Park
    • Taeg Kyu Kwon
  • View Affiliations

  • Published online on: May 1, 2003     https://doi.org/10.3892/ijo.22.5.1111
  • Pages: 1111-1116
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Abstract

Phorbol 12-myristate 13-acetate (PMA) is a protein kinase C (PKC) activator and tumor promoter that induces terminal differentiation in human myeloid leukemia cells. We undertook to characterize phorbol ester-activated PKC-mediated cell cycle arrest and apoptosis. In the present studies, we determined the effect of high intracellular levels of the anti-apoptosis Bcl-2 protein on caspase 3 activation and cyctochrome c release during phorbol ester 12-myristate 13-acetate (PMA)-induced apoptosis. For this, we used the U937 cells, Bcl-2 overexpressed U937 cells (U937/Bcl-2) and the PMA-resistant derivative cell line R-U937. The G1 arrest of U937 cells and U937/Bcl-2 cells induced by treatment with 20 nM PMA is associated with cyclin A down-regulation and accumulation of p21, cdks inhibitor. However, PMA had no effect on the levels of cyclin A expression and p21 expression under the same conditions of time and concentration of PMA in the R-U937 cells. Treatment with 20 nM PMA for 24 h produced morphological features of apoptosis and DNA fragmentation in U937 and U937/Bcl-2 cells, but not in R-U937 cells. This was associated with the caspase 3 activation and cyctochrome c release. R-U937 cells exhibited less cytochrome c release and sustained phosphorylation level of Akt during PMA-induced apoptosis. These findings indicate that R-U937 cells are resistant to PMA-induced apoptosis by a mechanism of the signaling defect in the activation of the caspase 3 that is involved in the execution of apoptosis.

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May 2003
Volume 22 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hah J, Lee K, Choi YJ, Kim W, Park J and Kwon TK: Inactive caspase 3 activates Akt in human leukemia cells susceptible or resistant to apoptosis induced by phorbol ester. Int J Oncol 22: 1111-1116, 2003
APA
Hah, J., Lee, K., Choi, Y.J., Kim, W., Park, J., & Kwon, T.K. (2003). Inactive caspase 3 activates Akt in human leukemia cells susceptible or resistant to apoptosis induced by phorbol ester. International Journal of Oncology, 22, 1111-1116. https://doi.org/10.3892/ijo.22.5.1111
MLA
Hah, J., Lee, K., Choi, Y. J., Kim, W., Park, J., Kwon, T. K."Inactive caspase 3 activates Akt in human leukemia cells susceptible or resistant to apoptosis induced by phorbol ester". International Journal of Oncology 22.5 (2003): 1111-1116.
Chicago
Hah, J., Lee, K., Choi, Y. J., Kim, W., Park, J., Kwon, T. K."Inactive caspase 3 activates Akt in human leukemia cells susceptible or resistant to apoptosis induced by phorbol ester". International Journal of Oncology 22, no. 5 (2003): 1111-1116. https://doi.org/10.3892/ijo.22.5.1111